Transdermal drug delivery technology for brain-targeted drug delivery / 药学学报

Intracerebral delivery of drugs for the treatment of central nervous system disorders is usually limited by the blood-brain barrier (BBB). Transdermal drug delivery systems (TDDS) have the advantage of improving patient compliance and avoiding first-pass effects compared to intravenous, oral and intranasal drug delivery, and are an emerging non-invasive drug delivery route that facilitates long-term drug delivery to patients. The discovery of direct subcutaneous targeting of lymphatic pathways to brain tissue has made TDDS a new brain-targeted drug delivery strategy. At the same time, the development of nano-delivery technology has further facilitated the application of TDDS for targeted drug delivery to the brain. This review summarizes the mechanism of transdermal drug delivery into the brain and the application of TDDS in the treatment of brain diseases, providing new ideas and methods for the treatment of central nervous system diseases.

Comparative effectiveness of different hepatocellular carcinoma screening intervals or modalities: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals.@*METHODS@#PubMed and other nine databases were searched through June 30, 2021. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Survival rates were also pooled using RR with 95% CIs because most eligible studies only provided the number of survival patients instead of hazard ratio.@*RESULTS@#In all, 13 studies were included. Two random controlled trials (RCTs) and six cohort studies compared screening intervals for ultrasonography (US) screening and found no significant differences between shorter (3- or 4-month) and longer (6- or 12-month) screening intervals in terms of early HCC proportion, HCC significant mortality, 1-year survival rate; screening at 6-month interval significantly increased the proportion of early HCC (RR = 1.17, 95% confidence interval [CI]: 1.08-1.26) and prolonged the 5-year survival rate (RR = 1.39, 95% CI: 1.07-1.82) relative to the 12-month interval results. Three other RCTs and two cohort studies compared different screening modalities in cirrhosis or chronic hepatitis B, which indicated no statistical differences in the proportion of early HCC (RR = 0.89, 95% CI: 0.40-1.96) and HCC mortality (RR = 0.69, 95% CI: 0.23-2.09) between the biannual US and annual computed tomography (CT screening). Biannual US screening showed a lower proportion of early HCC than biannual magnetic resonance imaging (MRI) (RR = 0.60, 95% CI: 0.37-0.97) and biannual US combined with annual CT (RR = 1.31, 95% CI: 1.13-1.51) screening. The proportion of early HCC in the contrast-enhanced US group was slightly higher than that in the B-mode US (RR = 1.08, 95% CI: 1.00-1.23) group.@*CONCLUSIONS@#The evidence suggests that 6 months may be the best HCC screening interval for US screening. The effectiveness of CT and MRI is better than US during same screening intervals. However, MRI and CT are more expensive than US, and CT also can increase the risk of radiation exposure. The selection of CT or MRI instead of US should be carefully considered.@*REGISTRATION@#No. CRD42020148258 at PROSPERO website ( https://www.crd.york.ac.uk/PROSPERO/ ).

Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.@*METHODS@#Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.@*RESULTS@#In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons.@*CONCLUSIONS@#Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.@*REGISTRATION@#PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.

Regulation of Wenjingtang on HIF-1α Expression and Mitochondrial Function of Ectopic Endometrial Stromal Cells in Patients with Endometriosis / 中国实验方剂学杂志

ObjectiveThis study investigated the mechanism of Wenjingtang in the prevention and treatment of endometriosis （EMT） from the perspective of regulating hypoxia stress and mitochondrial function. MethodPrimary human endometrial stromal cells （ESCs） form ectopic endometrial tissues were isolated and cultured， the cells were divided into control group （Control）， 5% control serum group （5% KBXQ）， 10% control serum group （10% KBXQ）， 5% Wenjingtang serum group （5% WJTXQ） and 10% Wenjingtang serum group （10% WJTXQ）. ESCs in different groups were detected for proliferation by methyl thiazolyl tetrazolium （MTT） assay， mRNA and protein expression of hypoxia inducible factor-1α （HIF-1α） by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis， mitochondrial ultrastructure by transmission electron microscope， mitochondrial function ［mitochondrial membrane potential， mitochondrial membrane potential（MMP） and cytochrome C（Cyt C） content］ and apoptosis （cell membrane permeability， nuclear fluorescence intensity， nuclear size and cell counts） by high content screening （HCS） assay， apoptosis rate by flow cytometry， and proteins of B-cell lymphoma-2 （Bcl-2） associated X （Bax）， Bcl-2 and cleaved cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3） by Western blot. ResultCompared with Control group， the 5% KBXQ and 10% KBXQ groups showed increased cell viability （P<0.01）， there was no significant change in HIF-1α mRNA and protein expression， transmission electron microscopy showed that the mitochondrial cristae were obvious and the inner and outer membranes of mitochondria were clear， HCS multichannel fluorescence staining showed that there were no significant changes in the expression of MMP， Cyt C and cell membrane permeability， and the nuclei showed uniform light staining， there were no significant changes in apoptosis rate， cleaved Caspase-3 protein expression and Bax/Bcl-2 ratio. Compared with Control group and corresponding concentration KBXQ group， the 5% WJTXQ and 10% WJTXQ group showed decreased cell viability （P<0.01） and HIF-1α mRNA and protein levels （P<0.05，P<0.01）， the ultrastructure of mitochondria was destroyed， some mitochondria were swollen and the cristae were blurred， moreover， decreased MMP and up-regulated Cyt C release （P<0.05，P<0.01）， increased cell membrane permeability （P<0.01）， and apoptosis characteristics included nuclear pyknosis， DNA agglutination in nucleus and decrease of cell numbers were observed （P<0.05，P<0.01）， increased apoptosis rate （P<0.01）， which was consistent with the results of HCS analysis， and up-regulated expression levels of cleaved Caspase-3 protein and Bax/Bcl-2 ratio （P<0.05，P<0.01）. ConclusionIn conclusion， the results suggest that Wenjingtang can improve hypoxia stress via down-regulating HIF-1α expression in ectopic ESCs， and inhibit cell proliferation， reduce mitochondrial biological activity and induce apoptosis， which might be the internal mechanism of Wenjingtang in preventing and treating EMT.

Research progress of pyruvate kinase type M2 in hepatocellular carcinoma / 中华肝脏病杂志

Primary hepatocellular carcinoma is one of the most common high-grade malignant tumors in the world. Its incidence ranks fifth among malignant tumors in China, and various therapeutic measures have poor curative effect. Pyruvate kinase type M2 is a key enzyme in the glycolytic pathway, and its abnormal expression in liver cancer is closely related to the proliferation, metastasis, diagnosis, treatment, prognosis, as well as drug and radiation resistance. Therefore, multi-pathway targeted regulation of pyruvate kinase type M2 use is expected to become a new direction for the treatment of primary liver cancer.

Current status of research on short-term urogenital function after transanal total mesorectal excision and laparoscopic total mesorectal excision / 中华胃肠外科杂志

Thanks to the new surgical approach, transanal total mesorectal excision (taTME) has a better operative field exposure than laparoscopic-assisted total mesorectal excision (laTME), especially for male patients with obesity, pelvic stenosis or prostate hypertrophy. Nevertheless, whether the urogenital function and quality of life after taTME are better as compared to laTME requires further study. According to the existing studies, taTME and laTME are not significantly different in symptoms of the urology system for male patients, but some large sample clinical studies show that the incidence of urethral mechanical injury after taTME is higher. Unfortunately, there is no elaboration on that for females. The sexual function of male patients after taTME and laTME is both impaired. The sexual function of male patients will be relieved to different degrees over time, but there is no significant difference. Compared with laTME, taTME shows advantages in the sexual function for female patients. There is no significant difference in short-term urogenital system function between taTME and laTME at present. As a new surgical approach, the impact on urogenital system function after taTME is acceptable. However, whether there is a significant difference in urogenital function between taTME and laTME needs further research. In addition, functional results still need comprehensive evaluation, and preoperative baseline evaluation also needs to be enhanced. The functional evaluation for male and female should be carried out separately rather than confused. Questionnaire for evaluation of functional results also needs to be verified.

Preparation and targeting capability of corona forming in human ovarian plasma / 药学学报

After entering the physiological environment, proteins and other biomolecules bind to the nanoparticles' surface, called protein corona. The corona establishes a new bio-interface that affects its physicochemical properties and biological behaviors. Variations in types and contents of human plasma proteins during the different physiological states can substantially change the composition and effects of the corona. With folic acid (FA)-modified polylactic acid-polyglycolic acid copolymer (PLGA) nanoparticles, the formation of protein coronas and their influence on the targeting capability are studied in healthy and ovarian human plasma. All human plasma samples were collected at the Peking University Third Hospital and this study protocol has been approved by Peking University Third Hospital Medical Science Research Ethics Committee (2019-409-1). Dynamic light scattering measurements demonstrated a 10-40 nm increase in their size distributions and a 30 mV decreased in their absolute zeta-potential since protein corona-coated PLGA-PEG and PLGA-FA were formed. The SDS-PAGE analysis showed the composition of the protein coronas from ovarian and healthy plasma in PLGA-FA were markedly distinct, particularly for proteins with molecular weight of 45, 110 and >180 kDa. Flow cytometry indicated that the absorption of ovarian plasma in PLGA-FA led to a lower cellular uptake by SKOV3 cells. Our results suggest that in vitro formed ovarian plasma protein corona could shield targeting molecules and reduced receptor-mediated internalization. The results of this pilot study will provide evidence of the effectiveness of active targeting nanoparticles under pathologic conditions. Additionally, the protein corona in different diseases is emerging as a key point; thus, a comprehensive understanding could accelerate clinical translation of functionalized nanoparticles.

Interpretation of international expert consensus guidance on indications, implementation and quality measures for transanal total mesorectal excision / 中华胃肠外科杂志

In recent years, transanal total mesorectal excision (taTME) has been a hot spot in the field of colorectal surgery. Compared with the traditional laparoscopic technique, taTME has potential advantages in the treatment of rectal diseases. However, the procedural safety and effectiveness of taTME need further verification. In order to ensure the safe and standardized implementation of this procedure, the European Society of Coloproctology, together with 14 international academic organizations related to colorectal surgery and minimally invasive surgery, has developed the international expert consensus guidance on indications, implementation and quality measures for taTME. This paper introduces the background of the international consensus guidance, and interprets its core contents, including the surgical indications (complex pelvic conditions, malignant and benign rectal diseases), surgical quality and outcome evaluation, structured training, and expert center. It is expected to provide reference and guidance for Chinese colorectal surgery colleagues performing taTME.

Research progress of ion channels relating to cerebral ischemic diseases and prevention and treatment with traditional Chinese medicine / 中国中药杂志

Cerebral ischemia is a series of clinical symptoms and signs of cerebral ischemia, hypoxia and neuronal damage caused by cerebral artery stenosis or occlusion due to atherosclerosis or thrombosis, which seriously affects human health and quality of life. Cerebral ischemia involves the cascade reaction of the "neurovascular unit" system, and finally affects the normal physiological function of nerve cells and produces a series of pathological changes. And the changes in the structure and function of various ion channels in the cell membrane play an important role during this process. This article illustrates the changes in the ion channel associated with ce-rebral ischemic diseases, such as the potassium ion channels, sodium ion channels, calcium channels and other relevant channels, like AQP, TRPM2, TRPM7, TRPV4, ASICs, Cl~- channel, and explores the intervention effect of traditional Chinese medicine in prevention and treatment of cerebral ischemic diseases from the perspective of ion channels, in order to provide references for potential targets involving in drug development for the future prevention and treatment of cerebral ischemic diseases.

Microdialysis sampling and HPLC-MS/MS quantification of sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rat blood and brain extracellular fluid / 药学学报

The treatment plan for chronic pain often proceeds from a single drug to drug combination therapy. Sinomenine and ligustrazine, natural alkaline substances derived from traditional Chinese medicines, are expected to provide a new choice for combination analgesic therapy strategies. Here we establish a microdialysis sampling and HPLC-MS/MS quantification method for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rat blood and brain extracellular fluid. Blood and brain microdialysis probes were implanted in the jugular vein toward the right atrium and left corpus striatum zone (AP +0.2 mm, ML 3.0 mm, DV 3.5 mm) in rats. The blood and brain microdialysis probes were perfused with citric acid buffer solution and Ringer's solution, respectively. Blood and brain extracellular fluid microdialysate were collected at intervals of 20 min at a perfusion rate of 1.5 μL·min-1, and continuously collected for 24 h after administration. The liquid chromatographic separation used a C18-reversed phase chromatographic column (HSS T3 2.5 μm, 2.1 mm×50 mm), the mobile phase was methanol/water (containing 0.05‰ formic acid), and gradient elution was carried out at a flow rate of 0.3 mL·min-1. Mass spectrometric detection used an electrospray ion source, positive ion mode and multi-reaction monitoring method. The selected quantitative ions for sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin, amitriptyline and internal standard naloxone were 330/181, 137/80, 172/154, 152/110, 160/142, 278/233 and 328/310 respectively. The specificity, linear range, matrix effect, accuracy, precision, stability and probe recovery were investigated and confirmed to be suitable for the determination of the above drugs in rat blood and brain extracellular fluid microdialysate. The calculated in vivo recovery of microdialysis probes ranged from 19.38% to 25.88%. After intravenous administration of sinomenine (50 mg·kg-1), ligustrazine (50 mg·kg-1), gabapentin (50 mg·kg-1), paracetamol (50 mg·kg-1), pregabalin (50 mg·kg-1) and amitriptyline (40 mg·kg-1) to rats, the peak concentration in the blood microdialysate was in the range of 0.2-10 μg·mL-1. Drug concentrations could also be detected in brain extracellular fluid microdialysate, however with lower levels (peak concentration: 0.1-6 μg·mL-1) than those of blood microdialysates at each time point. In conclusion, this method can be applied to microdialysis sampling and quantification of sinomenine, ligustrazine, gabapentin, paracetamol, pregabalin and amitriptyline in rats. The method will promote research in identifying herb-drug pharmacokinetic interactions, as well as safety concerns in combination-therapy strategies.

Advances in tumor microenvironment responsive and regulatory drug delivery system / 药学学报

The complexity of tumor microenvironment brings both challenges and opportunities for targeted drug delivery. On the one hand, using the special characteristic as stimuli, we can construct a variety of responsive drug delivery systems for tumor targeting. On the other hand, the abnormal vasculature and dense extracellular matrix in solid tumor become formidable barriers to the nanoparticles delivery, which greatly reduces the drug delivery efficiency. Lots of researches focus on regulating the tumor microenvironment to make it more conducive to drug delivery. In this review, we will highlight the recent advances both in tumor microenvironment responsive nano-drug delivery systems design and tumor microenvironment regulation to improve tumor targeted delivery efficiency, and discuss the existing problems and future development.

Effect and mechanism of Bidens pilosa decoction on non-alcoholic fatty liver induced by high fat and high glucose in mice / 中国中药杂志

This study aimed to investigate the effect and possible mechanism of Bidens pilosa decoction on non-alcoholic fatty liver disease(NAFLD) induced by high fat and high glucose in mice. Bald/c mice were randomly divided into normal group, model group, metformin(200 mg·kg~(-1)) treatment group, Bidens pilosa decoction(10 g·kg~(-1)) treatment group, metformin and B. pilosa decoction(100 mg·kg~(-1)+5 g·kg~(-1)) treatment group. Except for the normal group, mice in the other four groups were fed with high-fat and high-glucose diet for 8 weeks to establish the non-alcoholic fatty liver model. After 4 weeks of treatment, blood was collected from the eyeballs, the mice were sacrificed, and relevant indicators were detected. The results showed that compared with the model group, blood lipid and blood glucose levels of each treatment group were significantly lower(P<0.05); HE staining results showed that liver pathological damage in each treatment group was significantly improved; oil red O staining results showed fat distribution in each treatment group significantly reduced(P<0.01); immunohistochemical staining showed that glucose regulated the protein expression of protein 78(GRP78) in liver tissues of each treatment group was also significantly reduced(P<0.01); Western blot results showed that endoplasmic reticulum stress signal pathway-related factors GRP78, phosphorylated-protein kinase R-like ER kinase(p-PERK), eukaryotic translation-initiation factor 2α(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(Chop), inositol requiring 1α(IRE1α), and cleaved-cysteinyl aspartate specific proteinase 12(cleaved-caspase-12) were significantly reduced(P<0.01). The results of the combined drug treatment group were better than those of the single drug treatment group. These results showed that B. pilosa decoction had the effect in improving non-alcoholic fatty liver, and its mechanism may be related to the down-regulation of the expression of endoplasmic reticulum stress(ERS)-related factors, and the reduction of the apoptosis of hepatocytes caused by ERS and the down-regulation of blood lipid and blood glucose levels.

Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis / 生物医学与环境科学（英文）

Objective@#To evaluate the effects of incretin-based therapies on body weight as the primary outcome, as well as on body mass index (BMI) and waist circumference (WC) as secondary outcomes.@*Methods@#Databases including Medline, Embase, the Cochrane Library, and clinicaltrials.gov (www.clinicaltrials.gov) were searched for randomized controlled trials (RCTs). Standard pairwise meta-analysis and network meta-analysis (NMA) were both carried out. The risk of bias (ROB) tool recommended by the Cochrane handbook was used to assess the quality of studies. Subgroup analysis, sensitivity analysis, meta-regression, and quality evaluation based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) were also performed.@*Results@#A total of 292 trials were included in this study. Compared with placebo, dipeptidyl-peptidase IV inhibitors (DPP-4Is) increased weight slightly by 0.31 kg [95% confidence interval ( ): 0.05, 0.58] and had negligible effects on BMI and WC. Compared with placebo, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lowered weight, BMI, and WC by -1.34 kg (95% : -1.60, -1.09), -1.10 kg/m (95% : -1.42, -0.78), and -1.28 cm (95% : -1.69, -0.86), respectively.@*Conclusion@#GLP-1 RAs were more effective than DPP-4Is in lowering the three indicators. Overall, the effects of GLP-1 RAs on weight, BMI, and WC were favorable.

Accuracy of Xpert® MTB/RIF for the detection of tuberculosis and rifampicin-resistance tuberculosis in China: A systematic review and meta-analysis / 北京大学学报(医学版)

OBJECTIVE@#To systematically review the diagnostic accuracy of Xpert® Mycobacterium tuberculosis/rifampicin (Xpert® MTB/RIF) for the detection of active tuberculosis (TB) and rifampicin-resistance TB in Chinese patients.@*METHODS@#Four Chinese databases (SinoMed, CNKI, WanFang database, and VIP) and three English databases (PubMed, Embase, and The Cochrane Library) were searched from January 1, 2000 to September 15, 2017, to identify diagnostic tests about the accuracy of Xpert® MTB/RIF in Chinese patients. Two investigators screened the articles and extracted the information independently, and then the quality of each included study was evaluated by Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. Bivariate random-effects meta-analysis was conducted to pool the sensitivity and specificity. In addition, subgroup analyses were performed based on patient type (TB patient and TB suspected patient), sample type (sputum, bronchoalveolar lavage fluid and others). All statistical analyses were conducted with Stata version 13.0.@*RESULTS@#A total of 47 articles were included in this systematic review. Most of them (38 articles) were in Chinese and only 9 articles were in English. All the articles were published during 2014 to 2017, and the sample size ranged from 31 to 3 151. Forty articles including 42 comparisons about TB were finally included with the pooled sensitivity of 0.94 (95%CI: 0.92, 0.95) and the pooled specificity of 0.87 (95%CI: 0.84, 0.91). Subgroup analysis showed that different patient and specimen types had no significant differences on sensitivity, but the specificity of sputum group was higher than that of bronchoalveolar lavage fluid. As for the detection of rifampicin-resistant TB, 33 articles (38 comparisons) were analyzed, the pooled sensitivity and specificity were 0.92 (95%CI: 0.89, 0.94) and 0.98 (95%CI: 0.97, 0.99) respectively. There were no significant differences between the patient and specimen in the subgroup analyses. The Deeks funnel plot showed a possible publication bias for detecting active tuberculosis (P=0.08) and no publication bias for rifampicin-resistant TB (P=0.24). The likelihood ratio scatter gram showed that in clinical applications, Xpert® MTB/RIF had a good diagnostic ability for detecting active tuberculosis, and it had good clinical diagnostic value in detecting rifampicin-resistant TB.@*CONCLUSION@#Xpert® MTB/RIF has good sensitivity and specificity in detecting TB and rifampicin-resistant TB in Chinese people. In particular, it has good clinical value in diagnosing rifampicin-resistance TB.

Quality assessment of global guidelines on colorectal cancer screening / 北京大学学报(医学版)

OBJECTIVE@#To systematically review and assess the quality of guidelines on colorectal cancer screening worldwide to provide guidance for the development of high-quality colorectal cancer screening guidelines in mainland China.@*METHODS@#CNKI, WanFang Data, VIP, SinoMed, PubMed, Embase, and Web of Science were systematically searched to identify guidelines on colorectal cancer screening from inception to Jun. 20th, 2018, and so were some websites and major search engines about the development of the guidelines from the existing literature (search date: Aug. 3rd, 2018). Two experienced reviewers independently examined these abstracts and then extracted information, and the Appraisal of Guidelines for Research and Evaluation II (AGREE II) were used to evaluate the methodological quality of these guidelines by four well trained reviewers.@*RESULTS@#In this study, 46 guidelines published from 1994 to 2018 were finally included in our analysis from 10 countries and 5 regions, among which 5 were from mainland China. The quality of these guidelines was relatively high in domain 1 (scope and purpose) and domain 4 (clarity of presentation), and medium in domain 2 (stakeholder involvement). While in the other three domains (domain 3: rigour of development; domain 5: applicability; domain 6: editorial independence), the results were quite different among these guidelines. The quality of evidence-based guidelines (defined by the criteria based on World Health Organization guideline development handbook) was generally higher than that of the common guidelines. Existing guidelines from mainland China were not evidence-based guidelines, which were of low quality.@*CONCLUSION@#The colorectal cancer screening guidelines all over the world are generally large in number, low in quality, different in statements, and so are the guidelines in China. There are no evidence-based guidelines in mainland China, which cannot provide effective guidance for colorectal cancer screening, so we need to pay more attention to the establishment of guidelines with high quality and high credibility for colorectal cancer screening as well as for cancer screening based on the national condition, in order to provide reasonable guidance for practice in public health and improve the health conditions in our society.

Series of risk of bias assessment (5): Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) / 中华流行病学杂志

This paper summaries the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I),a tool for evaluating risk of bias about Non-randomized Studies-of Interventions (NRSI),and introduces the application of ROBINS-I in a published NRSI.According to the characteristics of NRSI,evaluation field and signaling question were designed in ROBINS-I to provide essential information about risk of bias for NRSI included in systematic reviews.ROBINS-I is the tool in assessment of risk of bias in observational studies and quasi-randomised studies.Although the tool hasbeen used in practice to some extent,but it still needs further improvement.Attention should be paid to its update and progress.

Series of risk of bias assessment (5): Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) / 中华流行病学杂志

This paper summaries the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I),a tool for evaluating risk of bias about Non-randomized Studies-of Interventions (NRSI),and introduces the application of ROBINS-I in a published NRSI.According to the characteristics of NRSI,evaluation field and signaling question were designed in ROBINS-I to provide essential information about risk of bias for NRSI included in systematic reviews.ROBINS-I is the tool in assessment of risk of bias in observational studies and quasi-randomised studies.Although the tool hasbeen used in practice to some extent,but it still needs further improvement.Attention should be paid to its update and progress.

Debridement, internal fixation, and reconstruction with titanium mesh for the surgical treatment of lumbar tuberculosis via a posterior-only approach in adults / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the clinical effects, indications and key techniques of debridement, internal fixation, and reconstruction with titanium mesh in lumbar tuberculosis via a posterior-only approach in adults.</p><p><b>METHODS</b>The clinical data of 26 patients with monosegment lumbar tuberculosis treated with surgery from March 2012 to March 2014 was retrospectively analyzed. Among them, 15 cases were male and 11 cases were female, and patients' age ranged from 21 to 68 years old (average, 44.7 years old). All patients suffered from back pain and/or pain with radiation to the legs. The clinical efficacy was evaluated based on the complications, erythrocyte sedimentation rate (ESR), imaging examination, and back and leg pain score of visual analogue scale (VAS).</p><p><b>RESULTS</b>All operations were successful in 26 patients with an average operation time of (2.4±0.8) h (range from 2 to 4 h), with an average blood loss of (320±86) ml(range from 200 to 700 ml) .VAS was decreased from (5.7±1.4) points preoperatively to (1.6±0.5) points 2 weeks postoperatively (<0.01); and ESR was decreased from (42.8±10.4)mm/h preoperatively to (12.1±5.6)mm/h 3 months after surgery (<0.01). All the patients were followed up for 24 to 48 months with an average of(28.3±5.8) months. One patients suffered from the recurrence of TB and sinus tract formation at 2 months after surgery, and was cured by stronger anti-tuberculosis drugs, local debridement with drainage, and sinus tract healed at 3 months after operation. All intervertebral bone graft obtained fusion within 1 year after operation and no local recurrence of TB was found at final follow-up.</p><p><b>CONCLUSIONS</b>Debridement, internal fixation, and reconstruction with titanium mesh via a posterior-only approach is a effective and safe method for the treatment of monosegment lumbar tuberculosis, especially for the patients with secondary spinal stenosis.</p>

Clinical efficacy and mechanism of total glucosides from white paeony for radioactive liver damage / 中国中药杂志

To discuss the effects of total glucosides from white paeony on preventing and treating radioactive liver damage, and explore its possible mechanisms. Thirty-six patients with primary hepatic carcinoma from 105th Hospital of Chinese PLA were treated with 3-dimensional conformal radiotherapy and randomly divided into simple irradiation group, total glucosides from white paeony group, and control group. The levels of AST, ALT, HA, LN, PCⅢ, CIV and TGF-β1 in serum of various groups were determined by using ELISA method. As compared with the simple irradiation group and control group, total glucosides from white paeony could obviously decrease the levels of AST, ALT, HA, LN, PCⅢ, CIV and TGF-β1(P<0.05, P<0.01). The results showed that the total glucosides from white paeony could effectively prevent and treat radioactive liver damage, and its mechanism might be associated with decreasing the levels of TGF-β1, and inhibiting the synthesis of collagen synthesis.

Legumain-responsive functional gold nanoparticles for drug targeting delivery and treatment of subcutaneous xenograft tumor / 药学学报

Legumain, a kind of asparaginyl endopeptidase, is overexpressed in highly metastatic and highly aggressive tumor, which can undergo an enzymatic hydrolysis of substrates. We proposed a legumain-responsive functional gold nanoparticle (GNP) drug delivery system (GNPs-A&C), which was consist of Ala-Ala-Asn-Cys-Lys (AK) modified GNPs (GNPs-AK) and 2-cyano-6-aminobenzothiazole (CABT) modified GNPs (GNPs-CABT). In the circulation system, the GNPs-A&C could passively target to the tumor site through the enhanced permeability and retention (EPR) effect. Then the overexpressed legumain specifically cleave the peptide to exposure the 1,2-thiolamino group, which could take place click reaction with the cyano group of CABT, leading to the aggregation of two GNPs, these aggregates of GNPs with increased size were more likely to retain within tumor site. In vivo fluorescent imaging demonstrated GNPs-A&C could acquire an enhanced accumulation in legumain-overexpressed C6 tumor. Importantly, after tethering DOX, the GNPs-DOX-A&C showed an excellent anti-tumor effect with reduced cardiotoxicity.